The compounds of the present invention are useful in the treatment and therapy of metabolic disorders of the blood, especially lipid and sugar metabolic disorders, through their ability to lower the triglyceride level and are therefore suitable for the prevention and treatment of type II diabetes and arteriosclerosis and the diverse diseased manifestations thereof.
Diabetes is a disease in which the body does not produce or properly use insulin.
Insulin is a hormone that is needed to convert sugar, starches and other food into energy needed for daily life. The cause of diabetes continues to be a mystery, although both genetics and environmental factors such as obesity and lack of exercise appear to play roles.
There are 20.8 million children and adults in the United States, or 7% of the population, who have diabetes. While an estimated 14.6 million have been diagnosed with diabetes, unfortunately, 6.2 million people (or nearly one-third) are unaware that they have the disease. Type 2 diabetes is the most common form of diabetes. In type 2 diabetes, either the body does not produce enough insulin or the cells ignore the insulin. Insulin is necessary for the body to be able to use sugar. Sugar is the basic fuel for the cells in the body, and insulin takes the sugar from the blood into the cells. When glucose builds up in the blood instead of going into cells, it can cause two problems:                Bodily tissues and the cells comprising them may be starved for energy.        Over time, high blood glucose levels may damage the eyes, kidneys, nerves or heart.        
Conditions associated with diabetes include hyperglycemia and hypoglycemia which will increase ones risk for many serious complications including heart disease (cardiovascular disease), blindness (retinopathy), nerve damage (neuropathy), and kidney damage (nephropathy). The present invention relates to substituted bicyclic 8-pyrrolidinobenzimidazoles and to the physiologically compatible salts and physiologically functional derivatives thereof.
United States Published Patent Appln. No. 2006/0148855 to MacDonald et. al. describes structurally similar carboxamide derivative compounds processes for preparing such compounds, pharmaceutical compositions comprising them and their use in the treatment of chronic and acute pain, itching and urinary incontinence.
A wide variety of carboxamide derivative compounds of different structures are known in the art, for example those disclosed in U.S. Pat. No. 5,461,075 to O'Neill et. al. and European Patent No. 0 401 903 to Martodam et. al., UK Patent Application Number GB 222631315 and International Patent Application, Publication Numbers WO 92/09285 to Brand, L., U.S. Pat. No. 7,084,176 to Morie et. al. and U.S Published Appln. No. 2004/138454. Particularly notable examples of carboxamide derivative compounds or Vanilloid receptor modulators are capsaicin or trans 8-methyl-N-vanillyl-6-nonenamide which is isolated from the pepper plant, capsazepine (Tetrahedron, 53, 1997, 4791) and olvanil or N-(4-hydroxy-3-20 methoxybenzyl)oleamide (J. Med. Chem., 36, 1993, 2595).
U.S. Pat. No. 6,723,730 to Bakthavatchalam et. al. discloses diaryl piperazine derivatives which bind with high selectivity and high affinity to vanilloid receptors, especially Type I Vanilloid receptors, also known as capsaicin or VR1 receptors. The compounds are said to be useful in the treatment of chronic and acute pain conditions, itch and urinary incontinence.
U.S. Published Appln. No. 2006/142333 to Rami et.al. discloses carboxamide derivatives as Vanilloid receptor modulators and their use for the treatment of chronic and acute pain conditions.
However, it is an object of the present invention to provide compounds and compositions comprising them for the therapeutic treatment of diabetes, hyperglycemia and other blood sugar related disorders through a metabolic blood sugar-lowering action.